Eif4g2, also known as DAP5, Nat1, or p97, is a eukaryotic translation initiation factor. It lacks binding sites for the 5' cap-binding protein eIF4E and is considered crucial for non-canonical translation initiation mechanisms, such as internal ribosomal entry sites (IRESs)-mediated cap-independent translation. It also contributes to scanning-based translation, helping ribosomes overcome obstacles like upstream open reading frames (uORFs) in long 5' UTRs of mRNAs from higher eukaryotes [2,3]. Eif4g2 is involved in various biological processes including learning and memory through its role in dendritic translation reprogramming [1].

In hepatocellular carcinoma (HCC), Eif4g2 deletion suppresses tumor growth and metastasis both in vitro and in vivo. It promotes HCC progression via IRES-dependent PLEKHA1 translation regulation [4]. In osteosarcoma, Eif4g2 identified from an RNA modification-related signature can promote tumor proliferation, migration, and M2 macrophage migration [5].

In conclusion, Eif4g2 is an important translation initiation factor involved in both normal biological processes like dendritic translation for learning and memory, and disease-related processes such as tumor progression in hepatocellular carcinoma and osteosarcoma. Studies using gene-knockout or knockdown models in these disease areas have revealed its potential as a therapeutic target, highlighting the importance of Eif4g2 in understanding disease mechanisms and developing new treatment strategies.